This invention relates to hemostatic compositions useful in the stemming or prevention of blood loss from surgical or traumatic wounds.
A hemorrhage of a blood vessel, body tissue, organ or bone can result in blood loss leading to hypovolemic shock and death. However, despite continued advances in trauma care, a significant number of trauma victims suffer fatal or severe hemorrhage every year. Many of these fatalities could be prevented if adequate means existed for on site control of blood loss. Hemophiliacs and patients receiving anticoagulant medication (e.g., during and/or after heart surgery) are also at high risk for rapid blood loss.
The use of fibrin as a coagulating substance for stopping bleeding and for sealing wounds has been widely accepted. Generally, such biological adhesives or "fibrin glues" are based on a two component system of fibrinogen and thrombin which when mixed form a fibrin coagulum by the cleavage of fibrinogen through the action of thrombin to form fibrin monomers that spontaneously polymerize to form a three dimensional network of fibrin. For example, Tisseel.TM. is a two-component kit containing a fluid thrombin component including calcium chloride and a somewhat more viscous fibrinogen component including factor XIII, fibronectin, aprotinin and plasminogen. The two components are delivered deep frozen in two separate syringes, or as two lyophilized powders with corresponding aprotinin and calcium solutions as solvents. Using this method, the fibrin glue consolidates when the two components are combined due to fibrin monomer aggregation. The setting rate is dependent on the thrombin concentration and varies from a few seconds (high thrombin concentration) to a couple of minutes (low thrombin concentration).
The major disadvantage of these preparations is that the water-like fluidity of the components renders them difficult to handle and administer. Although various efforts have been made to facilitate the administration of these compositions, for example, by the development of double-syringe applicators as described in U.S. Pat. No. 4,359,049, or a spray system as described in U.S. Pat. No. 4,427,651, the basic problem of low viscosity remains.
Wadstrom, U.S. Pat. No. 5,631,011 describes a method of increasing the viscosity of fibrin glue compositions by adding a biocompatible polymer capable of forming a viscous aqueous solution. The components of this system are provided in deep freeze solutions or as lyophilized powders which are diluted prior to use with aqueous solutions. The primary route of administration taught by Wadstrom is by a two component preparation. Thus, while Wadstrom emphasizes the advantages of increasing the viscosity of the solution over prior "water-like" fibrin glues, the components of this system still require additional preparation at the time of use. Wadstrom further teaches that compositions having a high viscosity are to be avoided because fibrin polymerization and adhesion to the tissues would be inhibited.
One currently used alternative to fibrin glue, is a biodegradable collagen patch ("TAF" patch). For example, Zimmerman and Schiele, U.S. Pat. No. 4,453,939, describe collagen carriers in the form of a foam, web or film that is coated with a mixture of blood-clotting components including fibrinogen and thrombin. To prevent reaction of the blood-clotting components prior to use, they are provided as a suspension in an organic solvent which is applied to the collagen by brushing, spraying or dipping. However, difficulties in achieving optimum timing for the fixing procedure have been reported using this method resulting in inconsistent attachment and stability of the active components onto the collagen carrier. Moreover, penetration of the active components beyond the surface of the collagen carrier is not possible using this method, thereby limiting the concentration of blood-clotting components available to the surface of the device. Another problem with the TAF patches is that the collagen fleece/foam used does not provide sufficient mechanical support once wet, preventing application of manual pressure to assist in stopping blood flow or repositioning of the patch once it has been applied to the wound. Further, surgeons have reported that the inflexibility of the TAF patch prevents them from easily conforming to the contours of the site to which they are applied. Still another problem with TAF patches is that they require refrigeration prohibiting use outside a clinic or hospital setting.
WO 96/17633 describes tissue sealants including a fibrin bandage. In the method used for generating the bandage, the active components are lyophilized in separate layers which are supported by an occlusive backing. Therefore, the active components are not homogeneously mixed throughout the bandage.
Accordingly, there is a need for hemostatic compositions that are sturdy enough to withstand manual pressure and which are less complicated to use, especially in emergency situations such as life-threatening traumas wherein stemming blood flow as fast as possible can be critical.